During postnatal growth, chondrocytes of the cartilaginous growth plates at the end of long bones proceed through a differentiation cascade initiated by stem cell clonal expansion as proliferative chondrocytes and ending with terminal differentiation during chondrocytic hypertrophy. In rapidly growing mammalian growth plates, chondrocytic enlargement during hypertrophy has been demonstrated to be the significant variable for understanding the cellular control mechanisms by which bones grow in length. In this proposal, volume regulation by growth plate chondrocytes will be investigated by: 1) measuring specific intracellular osmolytes that accumulate during volume increase, and analyzing the quantitative contribution of each to volume increase; and 2) examining the distribution of activity of specific transporters during volume increase in different zones of the growth plate, focusing first on the Na+/K+ pump. This proposal outlines experiments to initiate a systematic exploration of the multiple volume control regulatory mechanisms found in growth plate chondrocytes, and relates the results to an understanding of a fundamental question in growth plate biology-- chondrocytic control over differential growth rates through cellular swelling-by examining the interplay of multiple elements of both ionic and non-ionic volume control.